The proposed research is a study of the effects of low doses (sublethal) and repeated exposure to low doses of ultraviolet (UV, 254 nm) and ionizing radiation (X-rays) on cultured human diploid fibroblasts (HDF). Current emphasis is on defining the effects of these radiations on arrested nonmitotic populations of various HDF strains including the DNA repair-deficient xeroderma pigmentosum (XP) and ataxia telangiectasia (AT) strains and determining the rate and extent of DNA repair in these arrested populations. Another emphasis is on inducing with these radiations HDF transformants in culture. A fraction of cells from UV-irradiated arrested populations is lost upon subsequent incubation. The extent of cell loss is dose dependent and cell strain specific. Xeroderma pigmentosum strains are more sensitive to UV than are normal HDF. The sensitive target is DNA. The lethal event appears to be one on RNA transcription that leads to an inhibition of required protein synthesis. DNA excision repair proficient strains are more resistant to UV because they can remove to some extent the DNA damage that leads to an effect on RNA synthesis. Experiments to study the rate and extent of DNA repair in both UV and X-irradiated normal, XP, and AT populations of nondividing cells are proposed. The assay for repair is the loss of DNA sites sensitive to UV-specific or gamma-specific endonuclease. The objective is to gain from these rate studies an understanding of the mechanisms of excision repair in normal cells and some insight into the repair defects in the other strains. Other experiments to induce and detect HDF transformants in culture are proposed. Emphasis is placed on using HDF strains isolated from individuals with a predisposition to cancer, using fresh primary isolates, using single and multiple exposures to X-rays and UV with chemicals defined as co-carcinogens (phorbol esters, diethylstilbestrol, anthralin) and culture procedures that permit expression of a transformation event.